Mathematical modeling predicts that increased hsv-2 shedding in HIV-1 infected persons is due to poor immunologic control in ganglia and genital mucosa

Joshua T. Schiffer, David A. Swan, Amalia Magaret, Timothy W. Schacker, Anna Wald, Lawrence Corey

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

A signature feature of HIV infection is poor control of herpes virus infections, which reactivate from latency and cause opportunistic infections. While the general mechanism underlying this observation is deficient CD4+T-cell function, it is unknown whether increased severity of herpes virus infections is due primarily to poor immune control in latent or lytic sites of infection, or whether CD4+ immunodeficiency leads to more critical downstream deficits in humoral or cell-mediated immunologic responses. Here we compare genital shedding patterns of herpes simplex virus-2 (HSV-2) in 98 HIV infected and 98 HIV uninfected men matched on length of infection, HSV-1 serostatus and nationality. We demonstrate that high copy HSV-2 shedding is more frequent in HIV positive men, particularly in participants with CD4+ T-cell count <200/ L. Genital shedding is more frequent due to higher rate of shedding episodes, as well as a higher proportion of prolonged shedding episodes. eak episode viral load was not found to differ between HIV infected and uninfected participants regardless of CD4+ T-cell count. We simulate a mathematical model which recapitulates these findings and identifies that rate of HSV-2 release from neural tissue increases, duration of mucosal cytolytic immune protection decreases, and cell-free viral lifespan increases in HIV infected participants. These results suggest that increased HSV-2 shedding in HIV infected persons may be caused by impaired immune function in both latent and lytic tissue compartments, with deficits in clearance of HSV-2 infected cells and extracellular virus.

Original languageEnglish (US)
Article numbere0155124
JournalPloS one
Volume11
Issue number6
DOIs
StatePublished - Jun 2016

Bibliographical note

Funding Information:
This work was supported by National Institute of Allergy and Infectious Diseases grant P01 AI030731 to JTS, AM, and AW and grant K23 AI087206 to JTS. This funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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